ArticleLiterature Review

Does turmeric/curcumin supplementation improve serum alanine aminotransferase and aspartate aminotransferase levels in patients with nonalcoholic fatty liver disease? A systematic review and meta‐analysis of randomized controlled trials

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Abstract

We performed a meta‐analysis to evaluate the efficacy of turmeric/curcumin supplementation on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with nonalcoholic fatty liver disease (NAFLD). We searched PubMed, Scopus, Cochrane Library, ISI Web of Science, and Google Scholar up to November 20, 2018. Studies that examined the effect of turmeric/curcumin on serum concentrations of ALT and AST among patients with NAFLD were included. The mean difference and standard deviation (SD) of changes in ALT and AST between intervention and control groups were used as effect size for the meta‐analysis. A total of six randomized controlled trials (RCTs) were eligible for meta‐analysis. Results from pooled analysis revealed that turmeric/curcumin supplementation reduced ALT (MD: −7.31 UL/L, 95% CI [−13.16, −1.47], p = 0.014) and AST (MD: −4.68 UL/L, 95% CI [−8.75 −0.60], p = 0.026). When RCTs stratified on the basis of their treatment duration, the significant reduction in serum concentrations of ALT and AST was observed only in studies lasting less than 12 weeks. This review suggests that turmeric/curcumin might have a favorable effect on serum concentrations of ALT and AST in patients with NAFLD. However, further clinical trials are needed to confirm these findings.

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... considering the usage of curcumin or turmeric (Akbari et al., 2019; Goodarzi, Sabzian, Shishehbor, & Mansoori, 2019; Mansour-Ghanaei, Pourmasoumi, Hadi, & Joukar, 2018; Mousavi, Milajerdi, Varkaneh, Gorjipour, & Esmaillzadeh, 2020)[1,8,19,22] ; regular physical activity(Hashida et al., 2017) ...
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This study aims to equip health professionals with essential directions for their practice and research in fatty liver disease. In fatty liver disease, excess fat is accumulated in the liver cells, and it mainly has two types: Alcoholic Fatty Liver Disease (AFLD) and Non-Alcoholic Fatty Liver Disease (NAFLD). AFLD is widely accepted to be associated with excessive alcohol consumption. However, in NAFLD's case, although the name acknowledges that it is not associated with excessive alcohol consumption, the exact cause of NAFLD remains ambiguous. Furthermore, for almost four decades, without specialised treatments and prevention strategies, NAFLD has constantly increased, affecting more than a quarter of the world's population. Meanwhile, although the current dietary recommendations for NAFLD patients orbit around the conventional High-Carbohydrate Low-Fat diets, mounting evidence advocates the broader benefits of Low-Carbohydrate High-Fat (LCHF) diets in this regard. Therefore, focusing on the databases such as PubMed, Cochrane Library, and Google Scholar, the authors have carried out an advanced literature search reporting on the efficacy of LCHF diets on NAFLD. After a comprehensive search—using appropriate "keywords and Boolean operators" and "inclusion & exclusion criteria"—the authors selected a potentially relevant set of existing peer-reviewed articles for this narrative review. After critically investigating the LCHF-NAFLD theme, the authors found that LCHF diets may significantly decrease liver fat and may even reverse the disease by targeting the key causes of hepatic fat storage, i.e., high insulin levels, excessive calorie consumption (mainly from carbohydrates), and excessive consumption of refined carbohydrates. Additionally, LCHF diets may provide a comprehensive health benefit beyond liver health. The authors conclude that the LCHF- NAFLD theme represents a rich vein of research opportunities. The authors encourage and call researchers, doctors, nutritionists, dieticians, and related-health professionals to engage more with the LCHF-NAFLD theme.
... Curcuminoids are bioactive phenolic compounds and consist of more than 100 individual curcuminoids that have been isolated and identified from genus Curcuma, about 50 of which are present in C. longa (turmeric). Turmeric contains [43][44][45] Content courtesy of Springer Nature, terms of use apply. Rights reserved. ...
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Turmeric, the rhizome of Curcuma longa plant belonging to the ginger family Zingiberaceae, has a history in Ayurvedic and traditional Chinese medicine for treatment of chronic diseases, including metabolic and cardiovascular diseases (CVD). This parallels a prevalence of age- and lifestyle-related diseases, especially CVD and type 2 diabetes (T2D), and associated mortality which has occurred in recent decades. While the chemical composition of turmeric is complex, curcuminoids and essential oils are known as two major groups that display bioactive properties. Curcumin, the most predominant curcuminoid, can modulate several cell signaling pathways involved in the etiology and pathogenesis of CVD, T2D, and related morbidities. Lesser bioactivities have been reported from other curcuminoids and essential oils. This review examines the chemical compositions of turmeric, and related bioactive constituents. A focus was placed on the cellular and molecular mechanisms that underlie the protective effects of turmeric and turmeric-derived compounds against diabetes and CVD, compiled from the findings obtained with cell-based and animal models. Evidence from clinical trials is also presented to identify potential preventative and therapeutic efficacies. Clinical studies with longer intervention durations and specific endpoints for assessing health outcomes are warranted in order to fully evaluate the long-term protective efficacy of turmeric.
... Non-alcoholic fatty liver disease (NAFLD) is a chronic disease induced by triglyceride accumulation in liver cells (more than 5% of the liver weight) in the absence of significant alcohol consumption [1,2]. NAFLD begins with simple steatosis and progresses to nonalcoholic steatohepatitis, and then to severe liver lesions including cirrhosis, and even hepatocellular carcinoma [3]. ...
Article
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Curcumin is the principal polylphenol of turmeric that has been used to treat various disorders. However, its anti-obesity effects in patients with non-alcoholic fatty liver disease (NAFLD) remain controversial. Therefore, we aimed to perform a meta-analysis on the effects of supplementation with turmeric/curcumin on body weight, body mass index (BMI) and waist circumference (WC) in these patients. PubMed, Scopus, Cochrane Library, and ISI Web of Science were searched until January 2019, without any restrictions. Clinical trials that reported body weight, BMI and WC in patients with NAFLD were included. Weighted mean differences (WMDs) were pooled using a random-effects model. Eight studies (449 participants) fulfilled the eligibility criteria of the present meta-analysis. Overall, meta-analysis could not show any beneficial effect of turmeric/curcumin supplementation on body weight (WMD, -0.54 kg; 95% confidence interval [CI], -2.40, 1.31; p = 0.56; I2 = 0.0%), BMI (WMD, -0.21 kg/m2; 95% CI, -0.71, 0.28; p = 0.39; I2 = 0.0%) and WC (WMD, -0.88 cm; 95% CI, -3.76, 2.00; p = 0.54; I2 = 0.0%). Subgroup analysis based on participants' baseline BMI, type of intervention, and study duration did not show any significant association in all subgroups. The results showed that turmeric/curcumin supplementation had no significant effect on body weight, BMI and WC in patients with NAFLD. Further studies with large-scale are needed to find out possible anti-obesity effects of turmeric/curcumin.
... And it has been found the effect to decrease the cholesterol level in humans [17] and in rabbits which suggested the role to manage the cardiovascular disease [12]. Furthermore, it has been indicated the beneficial role of turmeric extract in other diseases and disorders including obesity, diabetes and liver disease [18][19][20][21]; whereas to the anti-inflammatory effects the immune system [22][23][24]. So, this study investigates the effect of the inclusion of turmeric powder in diets on fattening rabbits and some blood biochemical traits. ...
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Abstract. Thirty of weaned male rabbits of 4-5 weeks of age and average (534 ± 1.5g) in weight were divided into three treatments of 10 rabbits per treatment and used in 8 weeks feeding trial for production efficiency. The rabbits were fed one ration that contains crude protein (15.8%) and metabolizable energy (2865.5 Kcal/ Kg feed). The turmeric powder was added to the control ration at 4 or 8 gram/kg feed. (T1; control ration without turmeric powder, T2; control ration added 4 g turmeric powder/kg. feed and T3; control ration added 8 g turmeric powder/ kg.feed). Total gain, feed consumption rate and feed conversion ratio were calculated. The blood samples were obtained from the marginal ear vein from all rabbits at the end of the trail. Some blood biochemical parameters as total protein, triglyceride, cholesterol, and ALT, AST was studied. At the end of the trail, all rabbits were slaughtered, and some carcass traits as hot and cold carcass, dressing percentages, edible giblets were considered. The results indicated that adding Turmeric powder to fattening ration has significantly (p≤0.05) effect almost all production and blood traits. The total gain, total feed consumption, final weights, hot and cold carcass weights, dressing, blood traits cholesterol, and triglyceride were decreased significantly (p≤0.05). While TP and ALT, AST were not considerably (p≤0.05) for rabbits fed control ration added four and 8g Turmeric powder/kg. Supply as compared to control T1. Keywords: Rabbits, Turmeric powder, blood attributes.
... Curcumin treatment (1000 mg/day) significantly reduced serum levels of total cholesterol, LDL, triglycerides and uric acid in patients with non-alcoholic fatty liver disease (NAFLD) [66]. Additionally, several studies have demonstrated that curcumin reduces serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with NAFLD [67]. A similar effect of curcumin administration was observed in a randomized control trial where habitual drinkers with elevated serum transaminases and gamma-glutamyl transferase (GGT) levels [68] (68)(67)(66)(66)(65)(66)(66) [68]. ...
Article
Curcumin is the major bioactive polyphenolic ingredient of turmeric. Increasing evidence indicates that the health benefits of curcumin are mediated through its anti-inflammatory and antioxidant effects. Inflammasomes are essential components of inflammatory pathways that activate caspase-1 leading to pyroptosis and stimulate maturation and secretion of the proinflammatory cytokines, interleukin‐1β (IL-1β) and interleukin-18 (IL-18) through nuclear factor kappa-B (NF‐κB) signaling. The current review outlines the mechanisms of curcumin as an inflammasome modulator in inflammatory-related diseases. Regulation of NF‐κB signaling and interleukins secretion is the most prominent functional mechanism of curcumin in modulating inflammasomes. More importantly, curcumin can exert its anti-inflammatory role mainly through the down-regulation of NLRP3 inflammasomes. Given the fundamental role of inflammation in diseases, such as arthritis, cancer and cardiorenal disease, curcumin may have a pivotal therapeutic role through its ability to produce beneficial anti-inflammatory effects.
... And it has been found the effect to decrease the cholesterol level in humans [17] and in rabbits which suggested the role to manage the cardiovascular disease [12]. Furthermore, it has been indicated the beneficial role of turmeric extract in other diseases and disorders including obesity, diabetes and liver disease [18][19][20][21]; whereas to the anti-inflammatory effects the immune system [22][23][24]. So, this study investigates the effect of the inclusion of turmeric powder in diets on fattening rabbits and some blood biochemical traits. ...
Conference Paper
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Male rabbits are tested when turmeric powder was added to their daily food over 4-5 weeks. The food consists of 15.8% crude protein including 2865.5 Kcal/ Kg metabolizable energy. The test was carried over three sets of 10 rabbits. The turmeric was fed under a control process of 4 or 8 gram/kg. These groups are classified into T1: without adding nothing, including T2 and T3 with added turmeric with 4 and 8 gram/Kg respectively. The biochemical blood parameters of slaughtered rabbits are investigated and studied. Quite good results were achieved that approve the Turmeric powder has a direct influence on the production and blood traits when T1 and T2 feed control were applied and adopted.
... Despite the poor bioavailability of curcumin, a few recent meta-analyses described that curcumin/turmeric alleviated hepatic steatosis [201] and positivelyinfluencedliver-related outcomes, like ALT and AST (especially in doses higher than 1000 mg/day) [202,203]. Jalali et al. [204], in ameta-analysis (n-9 RCTs), aimed to investigate the effects of curcumin on NAFLD and concluded that curcumin-based interventions resulted in ALT, AST, TC, LDL, FBS, HOMA-IR, and serum insulin reduction, but had no effects on the TG, HDL, HbA1c, body weight, and BMI. ...
Article
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Non-alcoholic fatty liver disease (NAFLD) is a significant clinical and epidemiological problem that affects around 25% of the adult global population. A large body of clinical evidence highlights that NAFLD is associated with increased liver-related morbidity and mortality and an increased risk of cardiovascular disease, extrahepatic cancers, type 2 diabetes, and chronic kidney disease. Recently, a series of studies revealed the pivotal role of gut microbiota (GM) dysbiosis in NAFLD’s pathogenesis. The GM plays an essential role in different metabolic pathways, including the fermentation of diet polysaccharides, energy harvest, choline regulation, and bile acid metabolism. One of the most critical factors in GM stabilization is the diet; therefore, nutritional therapyappearsto be a promising tool in NAFLD therapy. This paper aims to review the current knowledge regardingthe nutritional approach and its implications with GM and NAFLD treatment. We discuss the positive impact of probiotics, prebiotics, and symbiotics in a reverse dysbiosis state in NAFLD and show the potential beneficial effects of bioactive substances from the diet. The full description of the mechanism of action and comprehensive examination of the impact of nutritional interventions on GM modulation may, in the future, be a simple but essential tool supporting NAFLD therapy.
... In this study, both prophylactic and therapeutic use of curcumin in NASH model significantly, reduced liver index, ALT and AST serum levels and AST/ALT ratio. This is in agreement with data obtained in other studies [94,95]. ...
Article
Backgrounds Modern dietary habits have been associated with Nonalcoholic Steatohepatitis (NASH). Curcumin is a natural herbal found to suppress cellular oxidative states and could be beneficial in NASH. This study investigates the effect of curcumin in an animal model of NASH. Materials and methods Fifty rats were allocated into five groups. Control, High Fat Diet (HFD), curcumin prophylactic (CP) and therapeutic (CT) groups. HFD regimen was given for 16 weeks. Curcumin was given along with HFD (prophylactic) or after establishment of the model for two weeks (therapeutic). Livers and blood samples were harvested for histological, biochemical, and molecular studies. Key findings Livers from HFD groups showed vascular, inflammatory, cellular degenerative and fibrotic changes. The hepatic damage was reflected by the increased serum liver enzymes. HFD groups showed excessive fibrotic change. Interestingly, curcumin administration as prophylactic or therapeutic significantly preserved and/or restored liver structure. This was evidenced by the normalization of the liver enzymes, preservation and/or reversibility of cellular changes and the decrease of the stage of fibrosis. Nuclear factor E2-related factor 2 gene (Nrf2) expression showed no changes in the HFD groups, however it showed upregulation in curcumin treated groups. Thus, the protective and therapeutic effect of curcumin could be induced through upregulation of the Nrf2 gene. Curcumin has a beneficial prophylactic and therapeutic effect that could hinder the development and/or treat NASH in susceptible livers. Significance Curcumin has a beneficial prophylactic and therapeutic effect that could hinder the development and/or treat NASH in susceptible livers.
... Anthocyanins (extracted from blackberries and blackcurrants) and resveratrol have beneficial effects in NAFLD patients thanks to their antioxidant potential, as observed by a decrease in triglyceride levels, suppression of hepatic steatosis and hepatocyte apoptosis, and reduction of hepatic inflammation and insulin resistance [27]. Cinnamon and turmeric are also believed to improve insulin sensitivity, decrease fasting glucose levels by reduction of hepatic gluconeogenesis, lower Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), improve lipid profile and decrease transaminase activity [28,29,45]. ...
Article
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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the developed world. Simple hepatic steatosis is mild, but the coexistence of steatohepatitis (NASH) and fibrosis increases the risk of hepatocellular carcinoma. Proper dietary and pharmacological treatment is essential for preventing NAFLD progression. The first-line treatment should include dietary intervention and increased physical activity. The diet should be based on the food pyramid, with a choice of products with low glycemic index, complex carbohydrates in the form of low-processed cereal products, vegetables, and protein-rich products. Usage of insulin-sensitizing substances, pro- and prebiotics, and vitamins should also be considered. Such a therapeutic process is intended to support both liver disease and obesity-related pathologies, including insulin resistance, diabetes, dyslipidemia, and blood hypertension. In the pharmacological treatment of NAFLD, apart from pioglitazone, there are new classes of antidiabetic drugs that are of value, such as glucagon-like peptide 1 analogs and sodium/glucose cotransporter 2 antagonists, while several other compounds that target different pathogenic pathways are currently being tested in clinical trials. Liver biopsies should only be considered when there is a lack of decline in liver enzymes after 6 months of the abovementioned treatment. Dietary intervention is recommended in all patients with NAFLD, while pharmacological treatment is recommended especially for those with NASH and showing significant fibrosis in a biopsy.
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PURPOSE: This study aimed to investigate the effect of turmeric intake alone or in combination with resistance training on liver enzymes in adult men who regularly consumed alcohol at least twice a week.METHODS: Twelve men (age: 36.0±5.26 years, weight: 99.9±17.9 kg, and height: 184.0±6.5 cm) were randomly assigned to the turmeric intake (2-3 g/day) alone (TI, n=6) group or the TI plus resistance training (60 minutes of RT 3 times a week) (TI+RT, n=6) group for 8 weeks. Blood was collected before and after 8 weeks of treatment. The analyzed variables included glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), γ-glutamyl transferase (γ-GTP), and GOT/GPT ratio.RESULTS:There was no significant interaction effect in all variables, but the main effect was found in all variables only in TI+RT group. The Cohen’s d effect size on the main effects of the TI+RT group on GOT (d=0.548), GPT (d=0.835), γ-GTP (d=0.623), and GOT/GPT ratio (d=0.800) ranged from 0.548-0.835, respectively. However, body composition such as percent body fat (%, p >.05) and muscle mass (kg, p >.05) did not show the main effect on time points as well as the interaction effect ( p >.05).CONCLUSIONS:Although the 8-week TI treatment did not show any statistically significant change, TI treatment showed a tendency to decrease in GOT, GPT, and γ-GTP, and the GOT/GPT ratio tends to increase. Therefore, there was a synergic effect of the TI plus RT treatment or the sum of the two treatments for 8 weeks.
Chapter
The rhizome of turmeric (Curcuma longa L.) has been used as an herbal medicine, coloring agent, spice, and food additive for thousands of years in different parts of the world particularly in Asian countries. It has been used for a range of diseases in many traditional medical schools, including Islamic traditional medicine, Chinese traditional medicine, and Ayurveda. It has been used mainly for digestive problems, as a cardio-, hepato-, and neuroprotective agent as well as in many inflammatory conditions such as arthritis and for enhancing immune system. Curcumin, a diarylheptanoid derivative found in turmeric, has anti-inflammatory, antioxidant, and anticancer properties; controls obesity and metabolic problems; and improves memory and mood disorders. Therapeutically, curcumin exhibits promising potential in preclinical and clinical studies and is currently in human trials for a variety of conditions, including metabolic syndrome, nonalcoholic fatty liver disease, rheumatoid arthritis, migraine, premenstrual syndrome, ulcerative colitis, knee osteoarthritis, polycystic ovarian syndrome, atherosclerosis, liver cirrhosis, amyotrophic lateral sclerosis, depression, psoriasis, and Alzheimer’s disease. Among all beneficial activities reported for curcumin, the research toward the obesity and metabolic-preventing/suppressing aspects of curcumin is growing. These findings emphasize that most of the traditional applications of turmeric is due to the presence of its key constituent, curcumin. According to the traditional background of turmeric use and clinical values of curcumin, further preclinical studies for unstudied properties and clinical studies with larger sample sizes for confirmed activities are expected.
Article
Background: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease characterized by excess accumulation of fat in hepatocytes. Because no drug has been approved for NAFLD treatment, this work analyzed the effects of agents resulting from 2 research hotspots, metabolic target agents, and natural plant drugs, on NAFLD with network meta-analysis. Methods: Public databases were searched through August 14, 2020. Randomized controlled trials that compared obeticholic acid, elafibranor, cenicriviroc, selonsertib, curcumin, silymarin, and resveratrol to placebo were included. Liver pathology improvement, hepatic biochemical indicators, and lipid metabolism indicators were analyzed. Results: Thirty-five studies were included in the meta-analysis. Obeticholic acid was found to significantly increase the frequency of liver biopsy improvement compared to placebo (OR: 2.10; 95% CI: 1.60, 2.77). The ranking results among the hepatic biochemical indicators showed that obeticholic acid (94.9%) and elafibranor (86.3%) have a relative advantage in reducing alanine aminotransferase (ALT) levels, and obeticholic acid also had an advantage (95.4%) in reducing aspartate aminotransferase (AST) levels. Considering lipid metabolic indicators, elafibranor (expSMD: 0.01; 95% CI: 0.00, 0.05; SUCRA: 100%), and obeticholic acid (expSMD: 0.48; 95% CI: 0.28,0.84; SUCRA: 75.6%) significantly reduced triglyceride (TG) levels compared with placebo; moreover, obeticholic acid, but not elafibranor, caused a serious increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a decrease in high-density lipoprotein cholesterol (HDL-C) levels. Conclusions: Novel metabolic targeted agents generally have better effects than natural plant drugs, especially obeticholic acid, and elafibranor. However, obeticholic acid showed serious adverse effects such as increasing LDL-C levels and decreasing HDL-C levels. Curcumin showed potential advantages for NAFLD but lacked statistical significance.
Article
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Article
Introduction Turmeric is a popular culinary spice and herbal remedy, and there is a growing body of research relating to its therapeutic use. However, it is not clear which preparations of turmeric are most effective and for which disorders. The aim of this paper was to conduct a meta-review of systematic reviews (SRs) to provide a status update for practitioners and researchers on the use of turmeric as a therapeutic option. Methods Reviews were selected that evaluated the use of oral turmeric products versus a placebo or standard care for the treatment of different health conditions. Two reviewers screened the SRs for inclusion, extracted and analysed the data. Review quality was assessed by R-AMSTAR and the quality of evidence expressed according to GRADE. Results Overall 65 SRs were retrieved covering 20 disease topics. There was moderate quality evidence to support the use of turmeric/curcumin for relieving pain and improving physical function in osteoarthritis. There was low quality evidence for its use in metabolic syndrome, inflammatory conditions and other diseases. The SR data suggested that whole turmeric and bioavailability-enhanced preparations may be useful for different conditions. Turmeric was safe and well tolerated. Conclusions There are multiple SRs that have examined the use of oral turmeric/curcumin for treating non-communicable diseases. Further primary studies on targeted patient groups would strengthen the evidence in areas that show most promise including osteoarthritis and metabolic syndrome. Future research should accommodate the complexity of turmeric medicines when designing studies to inform research and clinical decisions. This review was registered on PROSPERO CRD42018115813.
Article
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The beneficial effects of pomegranate have been shown on insulin resistance and obesity, which are linked to NAFLD pathogenesis. The aim of this study was to investigate the efficacy of pomegranate extract in patients with NAFLD. Forty-four NAFLD patients were randomly assigned to receive two pomegranate extract tablets or placebo for 12 weeks. Anthropometric measurements, serum lipids, glycemic indicators, and blood pressure were assessed at baseline and the end of the study. Pomegranate was associated with a reduction in the total cholesterol (p ˂ .001), triglyceride (p ˂ .001), low-density lipoprotein cholesterol (LDL-C)-to-high-density lipoprotein cholesterol (HDL-C) ratio (p ˂ .003), fasting blood sugar (p ˂ .001), homeostatic model assessment of insulin resistance (p = .02), diastolic blood pressure (p = .04), weight (p ˂ .001), body mass index (p ˂ .001), and waist circumference (p = .002), as compared to placebo. A significant increase was observed in serum HDL-C (p ˂ .001) after intervention with the pomegranate extract. However, no significant difference was shown between the two groups in serum insulin and LDL-C. The pomegranate extract supplement could be used as a complementary therapy along with existing therapies to improve glycemic indicators, serum lipids, anthropometric indices, and blood pressure in patients with nonalcoholic fatty liver.
Chapter
Turmeric (Curcuma longa) is a flowering plant of the ginger family with a long history of medicinal use due to its potent anti-inflammatory properties. Its most active constituent is curcumin, which has been widely studied. However, curcumin has extremely limited bioavailability. Thus, it is essential to add a little piperine (from black pepper) to any turmeric preparation, particularly curcumin, to allow for adequate absorption. Turmeric has antibacterial, fungistatic, and wound-healing properties. This chapter examines some of the scientific research conducted on turmeric, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of the herb’s use in treating ophthalmological, oral and dental, pulmonary, cardiovascular, cardiometabolic, gastrointestinal, genitourinary, musculoskeletal, neurological, and psychiatric disorders, among many others. Finally, the chapter presents a list of turmeric’s active constituents, different Commonly Used Preparations and Dosage, and a section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
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Multiphase pathological processes involve in Type 2 diabetes (T2DM)‐induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM‐induced NAFLD were investigated. T2DM‐induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM‐induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM‐induced production of interleukin 1 beta, interleukin 6, and TNF‐α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM‐induced NAFLD. In high D‐glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM‐induced NAFLD.
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Non-alcoholic fatty liver disease (NAFLD) is one of the most prevailing liver diseases worldwide. NAFLD is a defect at metabolic level that includes steatosis or hepatic fatty infiltration. Besides liver related mortality and morbidity, non-alcoholic fatty disease is also associated with serious complications of other organs, such as heart diseases. Objective: To assess the dietary patterns among patients suffering from fatty liver disease. Method: It was a cross sectional study conducted at Sir Ganga Ram Hospital and Shaikh Zayed Hospital, both are Tertiary care hospital of Lahore. Data was collected by self made questionnaire 270 patients were selected between the age of 19-65 years. A non probability convenient sampling technique was used and data was further analyzed by mean of SPSS v.25.0. Result: It was observed that 65.2% patients were consumers of cold drink, 56.4% patients were consumer of fatty food , 64.8% patients were skipping their meal.74.6% patients have no physical activity, 69.7%patients were overweight ,61% fatty liver patients were diabetic and 71.2% patients were not taking any type of supplements. Conclusion: Current study concluded that less physical activity, consumption of fatty food, cold drinks and less intake of nutritional supplements were responsible for this disease.
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Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The pathogenesis of this disease is closely associated with obesity and insulin resistance. Ginger can have hypolipidemic and antioxidant effects, and act as an insulinsensitizer. Objectives: The aim of this study was to evaluate the effects of ginger supplementation in NAFLD management. Patients and methods: In a randomized, double-blind, placebo-controlled clinical trial, 44 patients with NAFLD were assigned to take either two grams per day of a ginger supplement or the identical placebo, for 12 weeks. In both groups, patients were advised to follow a modified diet and physical activity program. The metabolic parameters and indicators of liver damage were measured at study baseline and after the 12 week intervention. Results: Ginger supplementation resulted in a significant reduction in alanine aminotransferase, γ-glutamyl transferase, inflammatory cytokines, as well as the insulin resistance index and hepatic steatosis grade in comparison to the placebo. We did not find any significant effect of taking ginger supplements on hepatic fibrosis and aspartate aminotransferase. Conclusions: Twelve weeks of two grams of ginger supplementation showed beneficial effects on some NAFLD characteristics. Further studies are recommended to assess the long-term supplementation effects.
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Background Since lifestyle changes are main therapies for non-alcoholic fatty liver disease (NAFLD), changing dietary components (nutritional or bioactive) may play a parallel important role. Few studies have assessed the effects of curcumin on NAFLD (mainly antioxidant and anti-inflammatory effects). We aimed to determine the effects of nano-curcumin (NC) on overweight/obese NAFLD patients by assessing glucose, lipids, inflammation, insulin resistance, and liver function indices, especially through nesfatin. Methods This double-blind, randomized, placebo-controlled clinical trial was conducted in the Oil Company Central Hospital, Tehran. 84 overweight/obese patients with NAFLD diagnosed using ultrasonography were recruited according to the eligibility criteria (age 25–50 yrs., body mass index [BMI] 25–35 kg/m²). The patients were randomly divided into two equal NC (n = 42) and placebo (n = 42) groups. Interventions were two 40 mg capsules/day after meals for 3 months. Lifestyle changes were advised. A general questionnaire, a 24-h food recall (at the beginning, middle and end), and the short-form international physical activity questionnaire (at the beginning and end) were completed. Also, blood pressure, fatty liver degree, anthropometrics, fasting blood sugar (FBS) and insulin (FBI), glycated hemoglobin (HbA1c), homeostasis model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), tumor necrosis factor-alpha (TNF-α), high sensitive c-reactive protein (hs-CRP), interleukin-6 (IL-6), liver transaminases, and nesfatin were determined at the beginning and end. Results NC compared with placebo significantly increased HDL, QUICKI, and nesfatin and decreased fatty liver degree, liver transaminases, waist circumference (WC), FBS, FBI, HbA1c, TG, TC, LDL, HOMA-IR, TNF-α, hs-CRP, and IL-6 (P < 0.05). The mean changes in weight, BMI, body composition (BC), and blood pressure were not significant (P > 0.05). After adjustment for confounders, the changes were similar to the unadjusted model. Conclusion NC supplementation in overweight/obese NAFLD patients improved glucose indices, lipids, inflammation, WC, nesfatin, liver transaminases, and fatty liver degree. Accordingly, the proposed mechanism for ameliorating NAFLD with NC was approved by the increased serum nesfatin and likely consequent improvements in inflammation, lipids, and glucose profile. Further trials of nano-curcumin’s effects are suggested. Trial registration Iranian Registry of Clinical Trials, IRCT2016071915536N3. Registered 2016-08-02.
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Non-alcoholic fatty liver disease (NAFLD) is a clinical condition characterized by lipid infiltration of the liver, highly prevalent in the general population affecting 25% of adults, with a doubled prevalence in diabetic and obese patients. Almost 1/3 of NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), and this can lead to fibrosis and cirrhosis of the liver. However, the main causes of mortality of patients with NAFLD are cardiovascular diseases. At present, there are no specific drugs approved on the market for the treatment of NAFLD, and the treatment is essentially based on optimization of lifestyle. However, some nutraceuticals could contribute to the improvement of lipid infiltration of the liver and of the related anthropometric, haemodynamic, and/or biochemical parameters. The aim of this paper is to review the available clinical data on the effect of nutraceuticals on NAFLD and NAFLD-related parameters. Relatively few nutraceutical molecules have been adequately studied for their effects on NAFLD. Among these, we have analysed in detail the effects of silymarin, vitamin E, vitamin D, polyunsaturated fatty acids of the omega-3 series, astaxanthin, coenzyme Q10, berberine, curcumin, resveratrol, extracts of Salvia milthiorriza, and probiotics. In conclusion, Silymarin, vitamin E and vitamin D, polyunsaturated fatty acids of the omega-3 series, coenzyme Q10, berberine and curcumin, if well dosed and administered for medium–long periods, and associated to lifestyle changes, could exert positive effects on NAFLD and NAFLD-related parameters.
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We performed a meta‐analysis to evaluate the efficacy of cumin supplementation on plasma lipid concentration in adult population. The search included PubMed, Scopus, ISI Web of Science, Google Scholar, and the Cochrane library (up to January 2018) to identify randomized controlled trials (RCTs) investigating the effects of cumin supplementation on serum lipid parameters. Mean difference (MD) was pooled using a random‐effects model. Meta‐analysis of data from six eligible RCTs with 376 participants showed a significant reduction in plasma concentration of total cholesterol (MD [95% CI] −10.90 [−21.39, −0.42] mg/dl, p = 0.042) and low‐density lipoprotein cholesterol (MD [95% CI] −6.94 [−11.53, −2.35] mg/dl, p = 0.003) after supplementation with cumin compared with control treatment, and plasma concentration of high‐density lipoprotein cholesterol (MD [95% CI] 3.35 [1.58, 5.12] mg/dl, p˂0.001) were found to be increased. Although our analysis indicated that cumin supplementation cannot change triglyceride (TG) concentration (MD [95% CI] −20.48 [−41.23, −0.26] mg/dl, p = 0.053), but after stratified the RCTs based on the primary level of TG (hypertriglyceridemia versus nonhypertriglyceridemia subjects), there was a significant decrease in nonhypertriglyceridemia subset. This systematic review and meta‐analysis suggested the efficacy of cumin supplementation on lipid parameters.
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Background Several studies reported that curcumin supplementation could improve non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the efficacy of curcumin/turmeric supplementation on liver enzymes in patients with NAFLD. Methods PubMed, Scopus, Web of Science and Google Scholar were systematically searched until December 2017. We included randomized controlled trials (RCTs) which examined effect of curcumin/turmeric supplementation on NAFLD in adult participants. Main outcome was alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Potential risks of bias (ROB) were assessed by using Cochrane ROB tool. Results All included studies showed low ROB in most of item of Cochrane ROB tool. Meta-analysis of 4 randomized controlled trials including 228 subjects showed a trend toward significant reduction of ALT blood concentrations in subgroup with ≥1000 mg/day curcumin supplementation (–11.36 IU/L, 95% CI: –22.75 to 0.02; I²:51%). Meta-analysis showed a significant reduction of AST in studies with 8-weeks administration (–9.22 IU/L, 95% CI: –12.77 to –5.67; I²: 49%). Conclusion This review suggests that curcumin/turmeric might have a favorable effect on NAFLD in higher dosage. Further high-quality studies with large-scale and higher dosage are warranted.
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Oxidative stress has been considered a key causing factor of liver damage induced by a variety of agents, including alcohol, drugs, viral infections, environmental pollutants and dietary components, which in turn results in progression of liver injury, non-alcoholic steatohepatitis, non-alcoholic liver disease, liver fibrosis and cirrhosis. During the past 30 years and even after the major progress in the liver disease management, millions of people worldwide still suffer from an acute or chronic liver condition. Curcumin is one of the most commonly used indigenous molecules endowed by various shielding functionalities that protects the liver. The aim of the present study is to comprehensively review pharmacological effects and molecular mechanisms, as well as clinical evidence, of curcumin as a lead compound in the prevention and treatment of oxidative associated liver diseases. For this purpose, electronic databases including "Scopus," "PubMed," "Science Direct" and "Cochrane library" were extensively searched with the keywords "curcumin or curcuminoids" and "hepatoprotective or hepatotoxicity or liver" along with "oxidative or oxidant." Results showed that curcumin exerts remarkable protective and therapeutic effects of oxidative associated liver diseases through various cellular and molecular mechanisms. Those mechanisms include suppressing the proinflammatory cytokines, lipid perodixation products, PI3K/Akt and hepatic stellate cells activation, as well as ameliorating cellular responses to oxidative stress such as the expression of Nrf2, SOD, CAT, GSH, GPx and GR. Taking together, curcumin itself acts as a free radical scavenger over the activity of different kinds of ROS via its phenolic, β-diketone and methoxy group. Further clinical studies are still needed in order to recognize the structure-activity relationships and molecular mechanisms of curcumin in oxidative associated liver diseases.
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Background: Dyslipidemia is an important and common cardiovascular risk factor in the general population. The lipid-lowering effects of turmeric and curcumin are unconfirmed. We performed a meta-analysis to assess the efficacy and safety of turmeric and curcumin in lowering blood lipids in patients at risk of cardiovascular disease (CVD). Methods: A comprehensive literature search was conducted on PubMed, Embase, Ovid, Medline and Cochrane Library databases to identify randomized controlled trials (published as of November 2016) that assessed the effect of turmeric and curcumin on blood lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the effect. Results: The analysis included 7 eligible studies (649 patients). Turmeric and curcumin significantly reduced serum LDL-C (SMD = -0.340, 95% confidence interval [CI]: -0.530 to -0.150, P < 0.0001) and TG (SMD = -0.214, 95% CI: -0.369 to -0.059, P = 0.007) levels as compared to those in the control group. These may be effective in lowering serum TC levels in patients with metabolic syndrome (MetS, SMD = -0.934, 95% CI: -1.289 to -0.579, P < 0.0001), and turmeric extract could possibly have a greater effect on reducing serum TC levels (SMD = -0.584, 95% CI: -0.980 to -0.188, P = 0.004); however, the efficacy is yet to be confirmed. Serum HDL-C levels were not obviously improved. Turmeric and curcumin appeared safe, and no serious adverse events were reported in any of the included studies. Conclusions: Turmeric and curcumin may protect patients at risk of CVD through improving serum lipid levels. Curcumin may be used as a well-tolerated dietary adjunct to conventional drugs. Further research is required to resolve uncertainties related to dosage form, dose and medication frequency of curcumin.
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Objectives Different studies have been conducted on the role of curcumin in health since having multiple properties, including antioxidant and anti-inflammatory effects. Due to the lack of studies regarding curcumin effects on obese patients with non-alcoholic fatty liver disease (NAFLD), our protocol was designed to assess nanocurcumin impacts on blood sugar, lipids, inflammatory indices, insulin resistance and liver function, especially by nesfatin. Setting This trial will be conducted in the Oil Company central hospital of Tehran, Iran with a primary level of care. Participants 84 obese patients with NAFLD diagnosed using ultrasonography will be employed according to the eligibility criteria‎. Interventions The patients will be randomly divided into two equal groups (nanocurcumin and placebo, two 40 mg capsules per day with meals for 3 months, follow-up monthly). Also, lifestyle changes (low-calorie diet and physical activity) will be advised. Measures of the primary and secondary outcomes A general questionnaire, 24 hours food recall (at the beginning, middle and end) and short-form International Physical Activity Questionnaire will be completed. Blood pressure, anthropometrics, serum sugar indices (fasting blood sugar and insulin, insulin resistance and sensitivity and glycosylated haemoglobin), lipids (triglyceride, total cholesterol and low-density and high-density lipoprotein-cholesterol, inflammatory profiles (interleukin-6, high-sensitivity C-reactive protein, and tumour necrosis factor-alpha), liver function (alanine and aspartate transaminase) and nesfatin will be measured at the beginning and end of the study. Conclusion This trial would be the first experiment to determine nanocurcumin efficacy on certain blood factors among obese patients with NAFLD. Nevertheless, studying the potential consequences of curcumin in various diseases, especially NAFLD, is required for clinical use. Trial registration number IRCT2016071915536N3; pre-results.
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Background: Despite the prevalence of nonalcoholic fatty liver disease in many countries still have not found a certain cure for it. Objective: So the purpose of this study was to survey the effect of curcumin supplementation with resistance training in patients with non-alcoholic fatty liver disease. Methods: In a randomized, controlled trial study, 45 patients with nonalcoholic fatty liver disease were divided into 4 groups (resistance training, curcumin supplement consumption, resistance training with curcumin supplement consumption, and placebo). The experimental groups performed a 12-week resistance training 3 days a week or consumed a curcumin capsule per day or both of them. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels before and after the protocol were measured. Data were analyzed by using ANCOVA with SPSS 22 software in P<0.05 level. Results: ALT and AST levels in resistance training and resistance training with curcumin supplement consumption significantly decreased (P<0.05) but in ALP levels significant differences was not seen (P>0.05). The grade of liver fat in any groups did not change significantly (P>0.05). Conclusion: On the basis of these results, we suggested that the Curcumin supplementation with resistance training in patient with nonalcoholic fatty liver disease could cause to improve liver function, but more studies must be conducted in this area with more subjects. Keywords: Curcumin, Liver enzymes, Resistance training
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Background Although several observational and experimental studies have examined the effects of low carbohydrate diets (LCDs) on nonalcoholic fatty liver disease (NAFLD), there are considerable inconsistencies among studies. We summarized the effect of LCDs on liver function tests, including intrahepatic lipid content (IHLC), alanine transaminase (ALT), aspartate aminotransferases (AST), and gamma-glutamyl transferase (GGT) in patients with NAFLD. Materials and Methods PubMed, ISI Web of Science, Scopus, and Google Scholar databases were searched for relevant publications until July 2014, resulting in ten relevant papers that were included in meta-analysis. Related articles were found by searching Medical Subject Heading terms of “NAFLD” in combination with “low carbohydrate”. For this meta-analysis, we used mean differences and standard errors of liver function biomarkers. Summary effect and corresponding confidence interval (CI) were estimated using random effect models. Heterogeneity between studies was assessed using Cochran's Q- and I-squared tests. Results Our search led to ten eligible papers that evaluated serum ALT levels (n = 238), nine reported serum AST levels (n = 216), five reported serum GGT concentrations (n = 91), and four assessed IHLC (n = 50). LCD decreased IHLC by −11.53% (95% CI: −18.10, −4.96; I² = 83.2%). However, the effect of LCD on liver enzymes was not significant. Mean differences for the effects of LCDs on ALT, AST, and GGT were −4.35 IU/L (95% CI: −12.91, 4.20; I² = 87.9%), −1.44 IU/L (95% CI: −4.98, 2.10; I² = 61.4%), and −7.85 IU/L (95% CI: −29.65, 13.96; I² = 99.4%), respectively. Conclusion LCD consumption in subjects with NAFLD led to a significant reduction in IHLC, but did not significantly affect the concentration of liver enzymes.
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Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Although many aspects of NAFLD pathogenesis have been understood, there is a paucity of effective treatments to be used as the second line when lifestyle modification is insufficient. Curcumin, a natural polyphenol from turmeric, has been shown to be effective against development of hepatic steatosis and its progression to steatohepatitis, yet these beneficial effects have not been explored in clinical practice. The aim of this study is to investigate the effects of curcumin on hepatic fat content as well as biochemical and anthropometric features of patients with NAFLD. In this randomized double-blind placebo-controlled trial, patients with ultrasonographic evidence of NAFLD were randomly assigned to receive an amorphous dispersion curcumin formulation (500 mg/day equivalent to 70-mg curcumin) or matched placebo for a period of 8 weeks. Liver fat content (assessed through ultrasonography), glycemic and lipid profile, transaminase levels, and anthropometric indices were evaluated at baseline and at the end of follow-up period. The clinical trial protocol was registered under the Iranian Registry of Clinical Trials ID: IRCT2014110511763N18. Compared with placebo, curcumin was associated with a significant reduction in liver fat content (78.9% improvement in the curcumin vs 27.5% improvement in the placebo group). There were also significant reductions in body mass index and serum levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glucose, and glycated hemoglobin compared with the placebo group. Curcumin was safe and well tolerated during the course of trial. Findings of the present proof-of-concept trial suggested improvement of different features of NAFLD after a short-term supplementation with curcumin. Copyright © 2016 John Wiley & Sons, Ltd.
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Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), is emerging as a main health problem in industrialized countries. Lifestyle modifications are effective in the treatment of NAFLD; however, the long term compliance is low. Therefore, several pharmacological treatments have been proposed but none has shown significant efficacy or long term safety. Natural polyphenols are a heterogeneous class of polyphenolic compounds contained in vegetables, which are being proposed for the treatment of different metabolic disorders. Although the beneficial effect of these compounds has traditionally related to their antioxidant properties, they also exert several beneficial effects on hepatic and extra-hepatic glucose and lipid homeostasis. Furthermore, natural polyphenols exert anti-fibrogenic and anti-tumoral effects in animal models, which appear relevant from a clinical point of view due to the association of NASH with cirrhosis and hepatocellular carcinoma. Several polyphenols, such anthocyanins, curcumin and resveratrol and those present in coffee, tea, soy are available in the diet and their consumption can be proposed as part of a healthy diet for the treatment of NAFLD. Other phenolic compounds, such as silymarin, are commonly consumed worldwide as nutraceuticals or food supplements. Natural antioxidants are reported to have beneficial effects in pre-clinical models of NAFLD and in pilot clinical studies, and thus need clinical evaluation. In this review we summarize the existing evidence regarding the potential role of natural antioxidants in the treatment of NAFLD and examine possible future clinical applications. This article is protected by copyright. All rights reserved.
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Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-related morbidity and mortality, but there is now growing evidence that NAFLD is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. For example, NAFLD increases risk of type 2 diabetes mellitus (T2DM), cardiovascular (CVD) and cardiac diseases, and chronic kidney disease (CKD). Although the primary liver pathology in NAFLD affects hepatic structure and function to cause morbidity and mortality from cirrhosis, liver failure and hepatocellular carcinoma, the majority of deaths among NAFLD patients are attributable to CVD. This narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease. The review discusses the factors involved in the progression of liver disease in NAFLD and the factors linking NAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD. The review will not discuss NAFLD treatments as these are discussed elsewhere in this issue of the Journal. For this review, PubMed was searched for articles using the keywords "non-alcoholic fatty liver disease" or "fatty liver" combined with "diabetes", "cardiovascular (or cardiac) disease", "cardiovascular mortality" or "chronic kidney disease" between 1990 and 2014. Articles published in languages other than English were excluded. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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Turmeric is a mild digestive, being aromatic, a stimulant and a carminative Turmeric is one of nature's most powerful healers. The active ingredient in turmeric is curcumin. Tumeric has been used for over 2500 years in India, where it was most likely first used as a dye. The medicinal properties of this spice have been slowly revealing themselves over the centuries. Long known for its anti-inflammatory properties, recent research has revealed that turmeric is a natural wonder, proving beneficial in the treatment of many different health conditions from cancer to Alzheimer's disease. An ointment base on the spice is used as an antiseptic in India. Turmeric water is an Asian cosmetic applied to impart a golden glow to the complexion. Curcumin has been shown to be active against Staphlococcus aureus (pus-producing infections). Anemia, cancer, diabetes, digestion, food poisoning, gallstones, indigestion, IBS, parasites, poor circulation, staph infections, and wounds. Turmeric decreases Kapha and so is used to remove mucus in the throat, watery discharges like leucorrhea, and any pus in the eyes, ears, or in wounds, etc. In Unani medicine, turmeric has been used for conditions such as liver obstruction and jaundice and has been applied externally for ulcers and inflammation. Roasted turmeric has been used as an ingredient of a preparation used for dysentery. Turmeric has also been used in tooth powder or paste. Turmeric has been used for many conditions in traditional medicine in India, Pakistan and Bangladesh. The rhizome is generally the part of the plant that is most widely used. It can be prepared in various ways and is reputed to alleviate asthma and coughs. Hot water extracts of the dried rhizome have been taken orally in Ayurvedic medicine to reduce inflammation. Turmeric is also regarded as a 'rasayana' herb, which is a branch of Ayurvedic medicine. Here turmeric is used to counteract ageing processes.
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Non-alcoholic fatty liver disease (NAFLD) is a growing health problem in both developed and developing countries. Metabolic abnormalities, specially insulin resistance and hyperglycemia are highly correlated with NAFLD. Lifestyle modifications including physical activity and promoting nutrient intakes are critical in prevention and treatment of NAFLD. Hence, in this article we aimed to review the evidence regarding the effects of various macronutrients on fat accumulation in hepatic cells as well as the level of liver enzymes. The relevant English and non-English published papers were searched using online databases of PubMed, ISI Web of Science, SCOPUS, Science Direct and EMBASE from January 2000 to January 2013. We summarized the findings of 40 relevant studies in this review. Although a hypocaloric diet could prevent the progression of fat accumulation in liver, the diet composition is another aspect which should be considered in diet therapy of patients with NAFLD. Several studies assessed the effects of dietary composition on fat storage in liver; however, their findings are inconsistent. Most studies focused on the quantity of carbohydrate and dietary fat; whilst there is very limited information regarding the role of protein intake.
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Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.
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Turmeric (Curcuma longa) is extensively used as a spice, food preservative and colouring material in India, China and South East Asia. It has been used in traditional medicine as a household remedy for various diseases, including biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism and sinusitis. For the last few decades, extensive work has been done to establish the biological activities and pharmacological actions of turmeric and its extracts. Curcumin (diferuloylmethane), the main yellow bioactive component of turmeric has been shown to have a wide spectrum of biological actions. These include its antiinflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. Its anticancer effect is mainly mediated through induction of apoptosis. Its antiinflammatory, anticancer and antioxidant roles may be clinically exploited to control rheumatism, carcinogenesis and oxidative stress-related pathogenesis. Clinically, curcumin has already been used to reduce post-operative inflammation. Safety evaluation studies indicate that both turmeric and curcumin are well tolerated at a very high dose without any toxic effects. Thus, both turmeric and curcumin have the potential for the development of modern medicine for the treatment of various diseases.
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Despite a history of purslane usage as a herbal treatment for dyslipidemia and hyperglycemia management, existing evidence from clinical trials is controversial. The aim for the current study was to evaluate the efficacy of purslane supplementation on lipid parameters and glycemic status in adult populations. A systematic review was conducted in PubMed, Scopus, ISI Web of Science, and Google Scholar up to January 15, 2018, searching for randomized controlled trials that assessed the impact of purslane on fasting blood glucose (FBG), triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Based on the detected heterogeneity between studies, a random- or fixed-effect model was applied in the meta-analysis. The findings from six randomized controlled trials, comprising 352 participants, indicated that purslane can reduce FBG (-4.54 mg/dl, 95% CI [-7.54, -1.53]; I2 = 0.53%) and triglycerides (-19.16 mg/dl, 95% CI [-38.17, -0.15]; I2 = 0%) levels. Changes in TC, LDL-C, and HDL-C concentrations did not reach a statistically significant level. Subgroup analysis showed a favorable effects of purslane on FBG, triglycerides, TC, and LDL-C in a subset of studies in which purslane was administered >1.5 g/day. Categorization based on gender showed that purslane was more effective in improving FBG, TC and LDL-C in females compared with males. This systematic review and meta-analysis suggested that the purslane might be effective on the improvement of blood lipid and glucose levels. Further robust studies with sufficient durations and dosages of supplementation are needed to confirm these results.
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Background: This systematic review and meta-analysis of randomized controlled trials (RCTs), were performed to determine the effects of curcumin intake on glycemic control and lipid profiles among patients with metabolic syndrome (MetS) and related disorders. Methods: We searched the following databases up until January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and evaluated for quality of the studies in accordance with the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (MDs) with 95% confidence intervals (95% CI). Results: Twenty-six trials with 1890 participants were included in the current meta-analysis. The findings demonstrated the significant association between curcumin intake and reduced fasting glucose levels (SMD -0.78; 95% CI, -1.20, -0.37; P<0.001), homeostasis model of assessment-estimated insulin resistance (SMD -0.91; 95% CI, -1.52, -0.31; P=0.003) and HbA1c (SMD -0.92; 95% CI, -1.37, -0.47; P<0.001). In addition, curcumin supplementation was significantly associated with triglyceride (SMD -1.21; 95 % CI, -1.78, -0.65; P<0.001) and total cholesterol reduction (SMD -0.73; 95 % CI, -1.32, -0.13; P= 0.01). However, curcumin intake significantly increased insulin levels (SMD 0.92; 95% CI, 0.06, 1.78; P=0.036). We found no significant effect of curcumin supplementation on LDL- (SMD -0.52; 95% CI, -1.14, 0.11; P=0.10) and HDL-cholesterol levels (SMD 0.28; 95% CI, -0.22, 0.77; P=0.27). Conclusion: Overall, curcumin consumption was associated with a significant reduction in fasting glucose, HOMA-IR, HbA1c, triglycerides and total cholesterol levels among patients with MetS and related disorders, but did not affect LDL- and HDL-cholesterol levels.
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This study aimed to evaluate the efficacy of green tea supplementation on nonalcoholic fatty liver disease treatment. Electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar, were systematically searched up to October 30, 2017, to identify eligible trials based on the inclusion criteria. The effect size was presented as mean difference with 95% confidence intervals (CI). The meta‐analysis of data from four studies indicated significant effects of green tea supplementation in altering alanine aminotransferases (−12.81 U/L; 95% CI: −18.17 to −7.45) and aspartate aminotransferases (−10.91 U/L; 95% CI: −19.66 to −2.17) blood concentrations. Likewise, a favorable effect of green tea administration was observed on body mass index (−2.08 kg/cm²; 95% CI: −2.81 to −1.36), triacylglycerol (−31.87 mg/dl; 95% CI: −40.62 to −23.12), total cholesterol (−27.57 mg/dl; 95% CI: −36.17 to −18.98), and low‐density lipoprotein cholesterol (−14.15 mg/dl; 95% CI: −23.69 to −4.60), whereas no significant effect was detected on high‐density lipoprotein cholesterol concentrations (7.41 mg/dl; 95% CI: −1.49 to 16.30) and homeostasis model assessment of insulin resistance (−4.06; 95% CI: −10.22 to 2.09). This systematic review and meta‐analysis of available trials suggests that there are potential benefits of green tea supplementation on nonalcoholic fatty liver disease.
Article
Objective: We systematically reviewed available randomized clinical trials (RCTs) to elucidate the overall effects of synbiotic supplementation in patients with nonalcoholic fatty liver disease (NAFLD). Methods: PubMed, Scopus, ISI Web of science and Google Scholar were searched up to December, 2017. All RCTs using synbiotic supplements to treat NAFLD included in this systematic review and meta-analysis. Mean Difference (MD) was pooled using a random-effects model. Results: Eleven eligible databases from seven RCTs were identified for the present meta-analysis. Our results showed that synbiotic supplementation can decrease body weight, fasting blood sugar, insulin, low density lipoprotein cholesterol, total cholesterol, triglyceride, high-sensitivity C-reactive protein, tumor necrosis factor alpha, alanine transaminase and aspartate transaminase levels among patients with NAFLD. In contrast, synbiotic did not have favorable effects on body mass index (BMI), waist circumference, homeostasis model assessment for insulin resistance (HOMA-IR), and high density lipoprotein cholesterol (HDL) levels compared with the placebo group. Conclusion: The current study revealed that synbiotic supplementation has favorable effect on inflammatory factors, liver enzymes and some anthropometric indices, lipid profiles and glucose homeostasis parameters in patients with NAFLD.
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Curcumin is the major constituent of turmeric (Curcuma longa). Turmeric has been widely used as a spice in foods and for therapeutic applications such as anti-inflammatory, antihyperlipidemic, and antimicrobial activities. Turmeric and curcumin are nonmutagenic and nongenotoxic. Oral use of turmeric and curcumin did not have reproductive toxicity in animals at certain doses. Studies on human did not show toxic effects, and curcumin was safe at the dose of 6 g/day orally for 4–7 weeks. However, some adverse effects such as gastrointestinal upsets may occur. Moreover, oral bioavailable formulations of curcumin were safe for human at the dose of 500 mg two times in a day for 30 days, but there are still few trials and more studies are needed specially on nanoformulations and it should be discussed in a separate article. In addition, curcumin is known as a generally recognized as safe substance. This review discusses the safety and toxicity of turmeric and curcumin in medicine. Turmeric and curcumin are nontoxic for human especially in oral administration. Turmeric and curcumin are also safe in animals. They are nonmutagenic and are safe in pregnancy in animals but more studies in human are needed.
Article
Background: To evaluate effects of turmeric (Curcuma longa L) and chicory seed (Cichorium intybus L) consumption on antioxidant status and inflammatory biomarkers in patients with non-alcoholic fatty liver disease (NAFLD). Methods: In this double-blind, randomized controlled clinical trial, 92 patients with NAFLD (46 males and 46 females) aged 20–60 year with body mass index (BMI) ranged 24.9-40 kg/m² were randomly assigned to 4 groups as follows: group TUR (n = 23) consumed 3 g/d turmeric; group CHI (n = 23) infused 9 g/d of powdered chicory seed; group TUR+CHI (n = 23) turmeric and chicory seed administered together (3 g/d turmeric + infused 9 g/d chicory seed); group PLA (n = 23) received placebo (6 × 500 mg corn starch capsules). Fasting blood samples, anthropometric measurements, physical activity and dietary records were collected at baseline and at the end of 12 weeks. All analyses were conducted on an intention-to-treat basis. Results: Significant decreases were observed in BMI of subjects in CHI and TUR + CHI groups, compared with PLA group (P < 0.05). Serum levels of total antioxidant capacity (TAC) were increased in TUR and CHI groups (P < 0.05 vs. PLA group). Chicory seed and combination of chicory seed and turmeric significantly reduced serum levels of malondialdehyde (MDA) in comparison with placebo (P < 0.05). Combination of turmeric and chicory seed marginally reduced serum level of Interleukin-6 (IL-6) (P = 0.058 vs. placebo). Conclusion: Turmeric and chicory seed may be applicable for reducing NAFLD risk factors.
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Nonalcoholic fatty liver disease (NAFLD) increases mortality from liver and heart disease and is the most important cause of hepatocellular carcinoma (HCC), which is rapidly becoming more common. Those having an increased fibrosis risk, cirrhosis or HCC should be identified amongst those with simple steatosis. Liver enzymes should always be determined at the yearly follow-up of patients with type 2 diabetes and those with the metabolic syndrome. Fatty liver should lead to an assessment of the risk of fibrosis by using a simple fibrosis test and to the referral of patients at risk by a specialist for diagnosis and treatment of NASH and fibrosis. NASH can only be diagnosed using a liver biopsy.
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Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver diseases, and is closely related to metabolic syndrome and its related conditions, diabetes mellitus and dyslipidemia. On the other hand, NAFLD as a multisystem disease increases the risk of several chronic diseases include type 2 diabetes mellitus, cardiovascular disease (CVD), and chronic kidney disease. The main objective was to review the efficacy of bioactive natural compounds assessed by clinical trials. Search literature using four databases (PubMed, EBSCO, Web of Science, and Ovid Medline) to review publications that focused on the impact of bioactive natural compounds in NAFLD treatment. Due to the lack of effective pharmacological treatments available for NAFLD, lifestyle modifications such as following a healthy diet, vigorous physical activity, and weight reduction remain the first line of treatment for NAFLD. However, due to the poor adherence to this type of treatment, especially for long-term weight loss diets some of which may have harmful effects on the liver, finding novel therapeutic agents for NAFLD treatment and/or preventing NAFLD progression has garnered significant interest. Although the therapeutic agents of NAFLD treatment have been reviewed previously, to date, no summary has been conducted of clinical trials examining the effects of herbal compounds on NAFLD-related biomarkers. This review highlights the beneficial role of herbal bioactives and medicinal plants in NAFLD treatment, particularly as complementary to a healthy lifestyle. All natural products described in this review seem to have some benefits to improve oxidative stress, cellular inflammation and insulin-resistance, which always remain as the "primum movens" of NAFLD pathogenesis.
Article
Objective: The aim of this systematic review and meta-analysis was to determine and clarify the impact of curcuminoids on serum lipid levels. Methods: Randomized controlled trials (RCTs) investigating the effects of curcuminoids on plasma lipids were searched in PubMed-Medline, Scopus, Web of Science databases (from inception to April 3rd, 2017). A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on lipid concentrations. Results: A meta-analysis of 20 RCTs with 1427 participants suggested a significant decrease in plasma concentrations of triglycerides (WMD: -21.36 mg/dL, 95% CI: -32.18, -10.53, p < 0.001), and an elevation in plasma HDL-C levels (WMD: 1.42 mg/dL, 95% CI: 0.03, 2.81, p = 0.046), while plasma levels of LDL-C (WMD: -5.82 mg/dL, 95% CI: -15.80, 4.16, p = 0.253) and total cholesterol (WMD: -9.57 mg/dL, 95% CI: -20.89, 1.75, p = 0.098) were not altered. The effects of curcuminoids on lipids were not found to be dependent on the duration of supplementation. Conclusion: This meta-analysis has shown that curcuminoid therapy significantly reduces plasma triglycerides and increases HDL-C levels.
Article
In recent decades, the pharmacological properties of numerous medicinal plants and opportunities in phytotherapy have been explored through research projects, reviews, and monographs. These studies confirm that medicinal plants offer new approaches to tackling diseases. However, improvement of phytotherapy in clinical practice relies on a number of critical factors. In particular, the studies are very heterogeneous, and results and their interpretation by healthcare workers vary greatly, so preventing consistency in clinical practice. There is therefore a lost opportunity to improve phytotherapy practice, because the work being done and the related systematic reviews cannot act as a body of data on which to base clear clinical recommendations. Approaches such as the Grading of Recommendations Assessment, Development and Evaluation or the Scottish Intercollegiate Guidelines Network methodology could easily help standardise the use of phytotherapy in clinical practice. In this context, evidence-based phytotherapy guidelines could offer new healthcare approaches to the treatment of diseases.
Article
Nonalcoholic steatohepatitis is a major cause of cirrhosis and liver cancer. It is associated with visceral adiposity and the metabolic syndrome and is nearly as common as type 2 diabetes. Metabolic stress, inflammation, and fibrosis are the primary pathogenic mechanisms.
Article
Objective: Insulin and leptin resistance are important risk factors for non-alcoholic fatty liver disease (NAFLD). There is limited evidence regarding the effects of turmeric on NAFLD. The aim of this study was to investigate the effects of turmeric supplementation on glycemic status and serum leptin levels in patients with NAFLD. Methods: This double-blind randomized controlled clinical trial was conducted on 46 patients with NAFLD (21males and 25 females) aged 20-60 years old and body mass index (BMI) between 24.9 and 40 kg/m2. The turmeric group (n = 23) was given six turmeric capsules daily for 12 weeks. Each capsule contained 500 mg turmeric powder (6×500 mg). The placebo group (n = 23) was given six placebo capsules daily for the same period. Fasting blood samples, anthropometric measurements, and physical activity levels were collected at the baseline and at the end of the study. Daily dietary intakes also were obtained throughout the study. Data were analyzed by independent t test, paired t test and analysis of covariance. Results: Turmeric consumption decreased serum levels of glucose, insulin, HOMA-IR and leptin (by 1.22, 17.69, 19.48 and 21.33% respectively, p < 0.05 for all) over 12 weeks compared with those variables in the placebo group. Changes in weight, BMI and liver enzymes were not significant compared to the placebo group. Conclusions: Turmeric supplementation improved glucose indexes and serum leptin levels and may be useful in the control of NAFLD complications.
Chapter
The metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that identify people at risk for diabetes and cardiovascular disease (CVD), while nonalcoholic fatty liver disease (NAFLD) is defined as a condition with excess fat in the liver due to nonalcoholic causes. Two key components of the MetS, glucose and triglycerides, are overproduced by the fatty liver. The liver therefore ultimately determines whether a person displays metabolic abnormalities. Both the MetS and NAFLD can occur in nonobese subjects, although their prevalence increases with obesity. Other acquired causes for both conditions include excessive intake of simple sugars and physical inactivity. NAFLD and MetS both predict type 2 diabetes, CVD, and nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Half of people with NAFLD carry at least one variant ([G]) allele at rs738409 in the PNPLA3 gene, which increases liver fat content. Such steatosis is not accompanied by features of the metabolic syndrome but it increases the risk of NASH, cirrhosis, and HCC, and thus identifies a common subtype of NAFLD.
Article
Objective Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by excess lipid deposition in the hepatic tissue and subsequent oxidative and inflammatory damage. Curcumin is a dietary polyphenol with lipid-modifying, antioxidant and anti-inflammatory properties. This study aimed to evaluate the efficacy and safety of supplementation with phytosomal curcumin in subjects with NAFLD. Methods Patients diagnosed with NAFLD (grades 1–3 according to liver ultrasonography) were randomly assigned to the curcumin (phytosomal form; 1 000 mg/day in 2 divided doses) (n=50) or placebo group (n=52) for a period of 8 weeks. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, hepatic enzymes, and liver ultrasonography were assessed at baseline and after 8 weeks of follow-up. Results 87 subjects (n=44 and 43 in the curcumin and control group, respectively) completed the trial. Supplementation with curcumin was associated with a reduction in body mass index (−0.99±1.25 vs. − 0.15±1.31 in the curcumin and placebo groups, respectively; p=0.003) and waist circumference (−1.74±2.58 vs. −0.23±3.49 in the curcumin and placebo groups, respectively; p=0.024). Ultrasonographic findings were improved in 75.0% of subjects in the curcumin group, while the rate of improvement in the control group was 4.7% (p<0.001). Serum levels of aspartate aminotransferase and alanine aminotransferase were reduced by the end of trial in the curcumin group (p<0.001) but elevated in the control group (p<0.001). Curcumin was safe and well tolerated during the course of trial. Conclusion Short-term supplementation with curcumin improves liver fat and transaminase levels in patients with NAFLD.
Article
Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4 weeks to 14 weeks. Curcumin was given at 100 mg/kg dose daily by oral gavage started at the age of 10 weeks and continued until 14 weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro-inflammatory cytokines, and chemokines including interferon (IFN) γ, interleukin-1β and IFNγ-inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF-κB) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican-3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1-NF-κB translocation.
Article
Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease. NAFLD is considered a multifactorial disease and a clinically relevant hepatic manifestation of metabolic syndrome. NAFLD is often accompanied by a constellation of metabolic and non-metabolic alterations, like dyslipidemia, insulin resistance in the liver and peripheral tissues, inflammation and oxidative stress; therefore, treatment of NAFLD should be directed at correcting all of these disturbances. The natural polyphenol curcumin has been the subject of increasing research for the treatment of NAFLD due to its lipid-modifying, antioxidant, anti-inflammatory, insulin-sensitizing, anti-steatotic, and anti-fibrotic properties. The therapeutic efficacy of curcumin has been demonstrated in several experimental models of NAFLD, however, clinical evidence is still scarce. The present review summarizes the current knowledge on the impact of curcumin supplementation on different biochemical and histopathological features of NAFLD.
Article
Systematic reviews and meta-analyses represent the uppermost ladders in the hierarchy of evidence. Systematic reviews/meta-analyses suggest preliminary or satisfactory clinical evidence for agnus castus (Vitex agnus castus) for premenstrual complaints, flaxseed (Linum usitatissimum) for hypertension, feverfew (Tanacetum partenium) for migraine prevention, ginger (Zingiber officinalis) for pregnancy-induced nausea, ginseng (Panax ginseng) for improving fasting glucose levels as well as phytoestrogens and St John's wort (Hypericum perforatum) for the relief of some symptoms in menopause. However, firm conclusions of efficacy cannot be generally drawn. On the other hand, inconclusive evidence of efficacy or contradictory results have been reported for Aloe vera in the treatment of psoriasis, cranberry (Vaccinium macrocarpon) in cystitis prevention, ginkgo (Ginkgo biloba) for tinnitus and intermittent claudication, echinacea (Echinacea spp.) for the prevention of common cold and pomegranate (Punica granatum) for the prevention/treatment of cardiovascular diseases. A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications. Nevertheless, potentially serious adverse events, including herb-drug interactions, have been described. This suggests the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population. Copyright © 2016 John Wiley & Sons, Ltd.
Article
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD) that leads to progressive liver disease and presents a growing challenge to public health. Because of the increased prevalence of metabolic syndrome and obesity, NAFLD and NASH have expanded to a substantial extent. In NASH patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH is mandatory. Although there is currently no validated test of serum biomarkers available to diagnose NASH, and histologic evaluation with a liver biopsy remains the gold standard, screening for fibrosis is recommended in patients with suspicion of NASH. Clinical prediction models and serum biomarkers for advanced fibrosis have relatively good negative predictive value and can be useful for screening. Also, transient elastography is increasingly available to estimate fibrosis in NASH. Therefore, due to the lack of a reliable and accepted non-invasive diagnostic modality, screening for NASH in the general population is not currently recommended. Better understanding of the natural history of NASH is needed to evaluate the utility and cost-effectiveness of screening.
Article
Background and aim: NAFLD is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression and outcomes of NAFLD and NASH. Methods: Pubmed/MEDLINE were searched from 1989-2015 for terms involving epidemiology and progression of NAFLD. Exclusions: selected groups (only morbidly obese or diabetics or pediatric), no data on alcohol consumption or other liver diseases. Incidence of HCC, cirrhosis, overall mortality and liver-related mortality were determined. NASH required histologic criteria. All studies were reviewed by 3 independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication and study population. We used random-effects models to provide point estimates (95% CI) of prevalence, incidence, mortality and incidence rate ratios, and meta-regression with sub-group analysis to account for heterogeneity. Results: Out of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (22.10-28.65) with highest prevalence in Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity [51.34% (41.38-61.20)], type 2 diabetes [22.51% (17.92-27.89)], hyperlipidemia [69.16% (49.91-83.46%)], hypertension [(39.34% (33.15-45.88)]] and metabolic syndrome [42.54% (30.06-56.05)] . Fibrosis progression proportion, measured in Brunt's score, and mean annual rate of progression in NASH were 40.76% (34.69-47.13) and 0.09 (0.06-0.12). HCC incidence among NAFLD patients was 0.44/1000 person-years (0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77/1000 person-years (0.33-1.77) and 11.77/1000 person-years (7.10-19.53), 15.44/1000 person-years (11.72-20.34) and 25.56/1000 person-years (6.29-103.80). Incidence Risk Ratios for liver-specific and overall mortality for NAFLD were 1.94 (1.28-2.92) and 1.05 (0.70-1.56). Conclusions: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous.f This article is protected by copyright. All rights reserved.
Article
Objective: The aim of this study was to systematically review the association of conjugated linoleic acid (CLA) consumption in two forms of foods enriched or supplemented with CLA on serum liver enzymes in human studies. Methods: We searched PubMed, Google Scholar, Cochrane Library, ScienceDirect, ProQuest, and Ovid up to January 2015. Studies that examined the effect of CLA supplementation or foods enriched with CLA on liver enzymes concentrations among healthy adults were included. The mean difference and SD of changes in serum liver enzymes between the intervention and control groups were used as effect size for the meta-analysis. Results: The analysis demonstrated that CLA supplementation led to slight and nonsignificant decreases in alkaline phosphatase (ALP) levels (mean difference [MD] -0.216; 95% confidence interval [CI], -0.60 to 0.17; P = 0.28). CLA intake can nonsignificantly increase alanine transaminase (ALT) levels (MD = 0.107 U/L; 95% CI, -0.29 to 0.244; P = 0.124) and can significantly increase aspartate aminotransferase (AST) levels (MD = 0.171 U/L; 95% CI, 0.034-0.307; P = 0.01). Subgroup analysis based on CLA source showed that CLA supplementation or foods enriched with CLA did not significantly alter ALT levels. Subgroup analysis showed that CLA supplementation led to significant increases in AST levels (MD = 0.224 U/L; 95% CI, 0.071-0.376; P = 0.004). However, foods enriched with CLA did not have any significant effects on AST levels. Conclusion: CLA supplementation was associated with a significantly increased circulating AST without any significant effect on ALP and ALT levels. Prospective studies are necessary to assess the clinical outcomes of the association between CLA and liver enzyme concentrations.
Conference Paper
Introduction: Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that may progress to end-stage liver disease. In rodents, pharmacologically active levels of curcumin are found in the liver following its ingestion and it has been shown to ameliorate many forms of hepatic insult including steatohepatitis and eliminates leptin’s effects on hepatic stellate cell activation. Objectives: The primary outcome measure was defi ned as a normalize ALT after effect of curcumin compare with placebo. Other aims were to compare effect on serum lipid profi le, fasting plasma glucose and to assess durability of ALT after discontinue curcumin. Design: A Randomized Double-blind Placebo- Controlled Trial. Methods: Population – Patients were recruited at GI clinic, Phramongkutklao hospital from 1/8/2010–1/8/2011 Inclusion criteria – Age between 18 and 80 yrs. – Elevate AST or ALT > 1.5 times on 2 occasions at least 3 month. – Ultrasound fi nding suggest fatty liver. – Doccument metabolic syndrome by modifi ed Asia-Pacifi c guideline of the NCEP III Exclusion criteria – History of daily alcohol consumption of more than 20 g/day. – Evidence of viral hepatitis or chronic liver disease such as autoimmune hepatitis, primary biliary cirrhosis, Wilson’s disease, hemochromatosis. – Decompensated liver disease. – Taking drug induced steatosis. Result: 53 patients were enrolled in the study. Ten patients were assigned to the curcumin group and 10 to the placebo group.Dermographic data were not difference signifi cant. Normalization or improvement of 25% or more in ALT levels from baseline was observed in curcumin group compared to 8% of those taking placebo but did not reach statistical signifi cance. (P = 0.572) Show in fi gure 2 Table 3 show drug-related severe adverse events occurred. Conclusion: Therapy with curcumin for 6 month resulted in not signifi - cant improvement of ALT and other laboratories of NAFLD patient with abnormal ALT compared to placebo but trend to normalized ALT in curcumin group.
Article
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily PPARα is highly expressed in liver, skeletal muscle, kidney, heart and the vascular wall. PPARγ is predominantly detected in adipose tissue, intestine and macrophages. PPARs are activated by fatty-acid derivatives and pharmacological agents such as fibrates and glitazones which are specific for PPARα and PPARγ respectively. PPARs regulate lipid and lipoprotein metabolism, glucose homeostasis, cell proliferation and differentiation, and apoptosis. PPARα controls intra- and extracellular lipid metabolisms whereas PPARγ triggers adipocyte differentiation and promotes lipid storage. In addition. PPARs also modulate the inflammatory response. PPAR activators have been shown to exert antiinflammatory activities in various cell types by inhibiting the expression of proinflammatory genes such as cytokines, metalloproteases and acute-phase proteins. PPARs negatively regulate the transcription of inflammatory response genes by antagonizing the AP-1, nuclear factor-KB (NF-κB), signal transducer and activator of transcription and nuclear factor of activated T-cells signalling pathways and by stimulating the catabolism of proinflammatory eicosanoids. These recent findings indicate a modulatory role for PPARs in inflammation with potential therapeutical applications in chronic inflammatory diseases.
Article
Nonalcoholic steatohepatitis (NASH) has been predicted to become the leading indication for liver transplantation (LT) in the United States (US). However, few studies have evaluated changes in the etiology of liver diseases among patients awaiting LT, and none have focused on the effects of NASH on LT waitlists in the US. We collected data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry from 2004 through 2013, on LT waitlist registrants with hepatitis C virus (HCV) infection, NASH, alcoholic liver disease (ALD), or a combination of HCV infection and ALD. We compared differences in survival within 90 days of registration (90-day survival) and probability of LT among patients with different diseases using Kaplan Meier and multivariate logistic regression models. Between 2004 and 2013, new waitlist registrants with NASH increased by 170% (from 804 to 2174), with ALD increased by 45% (from 1400 to 2024), and with HCV increased by 14% (from 2,887 to 3,291); registrants with HCV and ALD decreased by 9% (from 880 to 803). In 2013, NASH became the second-leading disease among LT waitlist registrants, after HCV. Patients with ALD had a significantly higher mean model for end-stage liver disease score at time of waitlist registration than other registrants. However, after multivariate adjustment, patients with ALD were less likely to die within 90 days when compared to patients with NASH (OR, 0.77; 95% confidence interval [CI], 0.67-0.89; P<.001); patients with HCV infection or HCV and ALD had similar odds for 90-day survival compared to NASH patients. Compared to patients with NASH, patients with HCV (OR, 1.45; 95% CI, 1.35-1.55; P<.001), ALD (OR, 1.15; 95% CI, 1.06-1.24; P<.001), or HCV and ALD (OR, 1.29; 95% CI, 1.18-1.42; P<.001) had higher odds for 90-day survival. Based on data from US adult liver transplantation databases, since 2004 the number of adults with NASH awaiting liver transplants has almost tripled. However, patients with NASH are less likely to undergo LT and less likely to survive for 90 days on the waitlist than patients with HCV, ALD, or HCV and ALD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
Article
The spice turmeric, derived from the rhizome of Curcuma longa L, has been used for centuries in food preparation and in traditional medicines to treat numerous diseases and conditions. The primary biologically active constituent of turmeric is the polyphenol, curcumin, an orange-yellow powder that has potent anti-inflammatory and antioxidant properties, which, in part, may contribute to curcumin's potential to prevent such conditions as cancer, Alzheimer disease, heart disease, and arthritis, to name a few. Clinical confirmation of these putative benefits is limited, however, and progress in establishing the in vivo efficacy in humans especially at typical dietary intakes is constrained by the poor bioavailability of this hydrophobic molecule. Strategies to improve absorption and distribution of curcumin in foods and findings from ongoing clinical studies should improve our understanding of how curcumin can best be used to improve human health.
Article
Diabetes is characterized by hyperglycaemia, which facilitates the formation of advanced glycation end-products (AGEs). Type 2 diabetes mellitus is commonly accompanied by non-alcoholic steatohepatitis, which could lead to hepatic fibrosis. Receptor for AGEs (RAGE) mediates effects of AGEs and is associated with increased oxidative stress, cell growth and inflammation. The phytochemical curcumin inhibits the activation of hepatic stellate cells (HSCs), the major effectors during hepatic fibrogenesis. The aim of this study was to explore the underlying mechanisms of curcumin in the elimination of the stimulating effects of AGEs on the activation of HSCs. We hypothesize that curcumin eliminates the effects of AGEs by suppressing gene expression of RAGE. Gene promoter activities were evaluated by transient transfection assays. The expression of rage was silenced by short hairpin RNA. Gene expression was analysed by real-time PCR and Western blots. Oxidative stress was evaluated. AGEs induced rage expression in cultured HSCs, which played a critical role in the AGEs-induced activation of HSCs. Curcumin at 20 µM eliminated the AGE effects, which required the activation of PPARγ. In addition, curcumin attenuated AGEs-induced oxidative stress in HSCs by elevating the activity of glutamate-cysteine ligase and by stimulating de novo synthesis of glutathione, leading to the suppression of gene expression of RAGE. Curcumin suppressed gene expression of RAGE by elevating the activity of PPARγ and attenuating oxidative stress, leading to the elimination of the AGE effects on the activation of HSCs. LINKED ARTICLE: This article is commented on by Stefanska, pp. 2209-2211 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2012.01959.x.
Article
Tacrolimus is a well-known potent immunosuppressant agent, which has various drug-drug or food-drug interactions. Previously, we found a renal transplant recipient who increased tacrolimus blood concentrations after ingestion of pomelo as a rare case. So, we investigated the effect of pomelo after its administration for one day or 3 consecutive days on the pharmacokinetics of tacrolimus in rats. We also confirmed the effects of grapefruit, turmeric, and ginger. The tacrolimus blood concentrations of the rats pre-treated with 100% pomelo juice were significantly higher than those pre-treated with water. On the other hand, the tacrolimus blood concentrations of the rats pre-treated with 50% pomelo juice were not significantly different from those pre-treated with water. The pomelo-tacrolimus interaction showed concentration dependency. Even low concentration of pomelo juice could enhance the blood concentrations of tacrolimus by repeated administration. The inhibitory effect of 100% pomelo juice disappeared 3 days after intake. The AUC values of tacrolimus in the rats pre-treated with grapefruit juice, ginger juice, and turmeric juice were significantly larger than those pre-treated with water. We could confirm the pomelo-tacrolimus interaction, which we discovered in a case study, quantitatively. We newly found the influence of turmeric and ginger on tacrolimus pharmacokinetics, comparable to pomelo.
Article
Worldwide, there is an epidemic of obesity and overweight, with two-thirds of Americans affected. A strong association exists between excessive body weight and nonalcoholic fatty liver disease (NAFLD), the most common etiology of abnormal liver function tests. Nonalcoholic fatty liver disease is a spectrum of liver disease, from a "bland" fatty infiltration to chronic hepatitis (nonalcoholic steatohepatitis or NASH), that can result in cirrhosis and organ failure. With the increasing prevalence of obesity in the world, the proportion of people affected by NAFLD is only expected to be parallel. Although primarily noted in obese individuals, NAFLD has also been associated with a number of surgical procedures, metabolic conditions, and medications. NASH is commonly underdiagnosed as most affected patients are symptom free, and routine screening is not performed. Noninvasive diagnostic testing is not sensitive in diagnosis or staging the severity of disease. Fatty infiltration and oxidative injury to the hepatocytes are believed to be the major factors behind the progression of disease from simple fatty infiltration of the liver to chronic hepatitis. Understanding the inflammatory pathways involved in NASH is a subject of extensive research. Currently, few proven treatment options exist, and controlled weight reduction is the only safe modality recommended for treatment of NASH.